{"doi":"10.1016/j.jbc.2025.108531","title":"The mechanism of peptidoglycan O-acetylation in Gram-negative bacteria typifies bacterial MBOAT-SGNH acyltransferases","abstract":"Bacterial cell envelope polymers are commonly modified with acyl groups that provide fitness advantages. Many polymer acylation pathways involve pairs of membrane-bound O-acyltransferase (MBOAT) and SGNH family proteins. As an example, the MBOAT protein PatA and the SGNH protein PatB are required in Gram-negative bacteria for peptidoglycan O-acetylation. The mechanism for how MBOAT-SGNH transferases move acyl groups from acyl-CoA donors made in the cytoplasm to extracellular polymers is unclear. Using the peptidoglycan O-acetyltransferase proteins PatAB, we explore the mechanism of MBOAT-SGNH pairs. We find that the MBOAT protein PatA catalyzes auto-acetylation of an invariant Tyr residue in its conserved C-terminal hexapeptide motif. We also show that PatB can use a synthetic hexapeptide containing an acetylated tyrosine to donate an acetyl group to a peptidoglycan mimetic. Finally, we report the structure of PatB, finding that it has structural features that shape its activity as an O-acetyltransferase and distinguish it from other SGNH esterases and hydrolases. Taken together, our results support a model for peptidoglycan acylation in which a tyrosine-containing peptide at the MBOAT's C-terminus shuttles an acyl group from the MBOAT active site to the SGNH active site, where it is transferred to peptidoglycan. This model likely applies to other systems containing MBOAT-SGNH pairs, such as those that O-acetylate alginate, cellulose, and secondary cell wall polysaccharides.","journal":"Journal of Biological Chemistry","year":2025,"id":539303,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9463,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1056496,"name":"Bailey J. Schultz","orcid":"0000-0002-4648-0172","position":1,"is_corresponding":false},{"id":1056497,"name":"Eric Snow","orcid":"0000-0002-7464-8323","position":2,"is_corresponding":false},{"id":1333901,"name":"Ashley S. Brott","orcid":"0000-0002-7425-9475","position":3,"is_corresponding":false},{"id":1333902,"name":"Stefen Stangherlin","orcid":"0000-0002-2953-4730","position":4,"is_corresponding":false},{"id":1333903,"name":"Tyler Malloch","orcid":"0009-0001-2386-7155","position":5,"is_corresponding":false},{"id":1333904,"name":"J London","orcid":"0009-0005-5499-3962","position":6,"is_corresponding":false},{"id":260812,"name":"Suzanne Walker","orcid":"0000-0002-0545-914X","position":7,"is_corresponding":false},{"id":452940,"name":"Anthony J. Clarke","orcid":"0000-0003-4076-0488","position":8,"is_corresponding":false},{"id":452939,"name":"Alexander C. Anderson","orcid":"0000-0002-1870-2903","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T02:52:30.048313Z","pmid":"40280421","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}